High energy liquid enteral nutritional composition

ABSTRACT

High energy and high protein liquid nutrition enteral compositions are provided that contain micellar casein and caseinate, an optionally a small amount of whey.

CROSS-REFERENCE TO RELATED APPLICATIONS

This is a Continuation of U.S. patent application Ser. No. 14/632,918,filed Feb. 26, 2015, which is a Continuation of U.S. patent applicationSer. No. 13/843,330, filed Mar. 15, 2013, now U.S. Pat. No. 8,999,423,which is a Continuation of U.S. patent application Ser. No. 12/746,490,filed as the U.S. National Stage application of PCT/NL2008/050777, filedDec. 5, 2008, now U.S. Pat. No. 8,409,651, which claims the benefit andpriority of International Application No. PCT/NL2007/050626, filed Dec.5, 2007; European Patent Application No. 08157877.5, filed Jun. 9, 2008;U.S. Provisional Application No. 61/059,865, filed Jun. 9, 2008; andEuropean Patent Application No. 08169152.9, filed Nov. 14, 2008. Theforegoing applications are incorporated by reference herein in theirentirety.

FIELD OF THE INVENTION

The present invention is in the field of liquid enteral nutritionalcompositions.

BACKGROUND OF THE INVENTION

The present invention relates in general to a liquid enteral compositionfor providing nutrition, either as a supplement, or as a completenutrition, with a high energy content.

The human body requires energy to perform its vital functions, such asblood circulation, immune processes, respiration processes, etc. Energycan be supplied in the form of calories. Calories are typically suppliedby the consumption of food. Calorie sources can be classified into threecategories: proteins, fats, and carbohydrates. Proteins can provide thebody with support for muscular activity, fats can provide the body withstored energy, and carbohydrates can supply the body with immediateenergy. Essential vitamins and minerals are necessary to help regulatethe processes of the human body.

A person should receive a proper balance of nutrients to sustain health,otherwise, malnutrition can result in a variety of physicalcomplications. Moreover, it is imperative that the support provided beadapted to the needs of a person. For example, patients who are ill,require increased and specialized nutritional support. An increase inspecific nutrients can help the body recover from a particular stressplaced upon it, such as sport, emotional and labour stress, illness,medical surgery, malnutrition, etc.

Nutritional needs can also change with a person's age. For example,elderly persons show a decrease in the amount of energy their bodyrequires from fat sources.

In this respect, it is submitted that in the context of thisapplication, an elderly person is a person of the age of 50 or more, inparticular of the age of 55 or more, more in particular of the age of 60or more, more in particular of the age of 65 or more. This rather broaddefinition takes into account the fact that the average age variesbetween different populations, on different continents, etc. Mostdeveloped world countries have accepted the chronological age of 65years as a definition of ‘elderly’ or older person (associated with theage at which one may begin to receive pension benefits), but like manywesternized concepts, this does not adapt well to e.g. the situation inAfrica. At the moment, there is no United Nations (UN) standardnumerical criterion, but the UN agreed cut-off is 60+ years to refer tothe older population in Western world. The more traditional Africandefinitions of an elder or ‘elderly’ person correlate with thechronological ages of 50 to 65 years, depending on the setting, theregion and the country.

Because at least certain persons may not receive their requirednutritional support from a normal diet, or may not be able to eat normalfood, nutritional compositions, such as nutritional supplements andcomplete nutrition have been designed to provide nutritional support topersons in need thereof. This nutrition can be directed towards aparticular type of nutritional support. For example, a supplement mayprovide a person with additional calories for increased energy. Althoughthese supplements provide a certain amount of nutritional support, it isin the best interests to provide a nutritional composition havingincreased nutritional value for a specific nutritional requirement. Inthe above examples of elderly persons and ill patients, it is desired toprovide nutritional liquid compositions having increased energy as wellas increased protein per unit dosage.

In this regard, although an elderly person's energy needs may bereduced, their ability to consume products may also be diminished. Forexample, they may have difficulty consuming a product due to, e.g.,swallowing difficulties, or due the too large amount of product theyneed to consume to meet the daily intake of nutrients. Hence, complianceis not optimal, and often, the intake is suboptimal, leading tosuboptimal nourishment.

Further, certain disease states or conditions may require restrictionson the diet a patient consumes. For example, renal patients may havefluid restrictive diets.

Also, a number of patients need nutrition in the smallest volume ofliquid. These patients may be cachectic patients or persons sufferingfrom end-stage AIDS, cancer or cancer treatment, severe pulmonarydiseases like COPD (Chronic Obstructive Pulmonary Disease), tuberculosisand other infection diseases or persons that experience severe surgeryor trauma like burns. Furthermore, persons suffering from disorders inthe throat or mouth such as oesophageal cancer or stomatitis and personshaving problems with swallowing like dysphagic persons, require specialliquid, low-volume nutrition. Also, persons suffering from reducedappetite and/or loss of taste will benefit from a low-volume liquidnutritional composition.

Therefore, a need exists for improved enteral compositions, with anincreased amount of protein and calories per unit volume for an elderlyperson or ill patient.

However, increasing calories and/or proteins in a nutritional liquidcomposition may increase the overall viscosity of the composition. Thiscan make the liquid nutritional composition difficult to consume oradminister, and can also diminish the taste of the nutritionalcomposition. Furthermore, technical difficulties exist in producing astable, in particular a shelf-stable nutritional liquid compositionhaving a high content of proteins.

The problem of the present invention is therefore to provide a stable,attractive, liquid enteral composition for providing nutrition, eitheras a supplement, or as a complete nutrition, with a high energy content,to a person, in particular to an elderly person or an ill patient.

PRIOR ART

WO 02/098242 A1 (Nestle, 12 Dec. 2002) discloses a calorically denseliquid oral supplement (2.25 kcal/ml) based on a (60:40) soy proteinisolate/caseinate mixture with a protein level of 9 g/100 ml (16 En %),12.25 g/100 ml of fat (49 En %), and 19.7 g/100 ml of digestiblecarbohydrates (35 En %).

U.S. Pat. No. 5,683,984 (Nestec S. A.) and the corresponding EP patent 0686 396 B1 teach to replace all of the caseinate in a medium energynutritional formulation (1 kcal/ml) by native micellar casein to obtaina formulation essentially containing native micellar casein with a lowviscosity and a thermal stability to withstand sterilization. Itdiscloses a composition containing a maximum of 7 vol % of nativemicellar casein. However, the latter document does not teach to replaceonly part of the caseinate by native micellar casein in a high energyhigh protein nutritional formulation and the problems that would arisein doing so, nor does it teach the poor shelf and heat stability, normeasures to overcome said problems with the formulations according toour invention.

The commercially available product RESOURCE® 2.0 is a high calorieproduct from Novartis (2 kcal/ml), based on a mixture of calcium andsodium caseinate as protein source, comprising 9 g/100 ml of proteins(18 En %), 8.7 g/100 ml of fat (39 En %), and 21.4 g/100 ml ofdigestible carbohydrates (43 En %), and is provided in a 237 ml unitdosage.

The commercially available product VHC® 2.25 is a high calorie productfrom Nestle (2.25 kcal/ml), based on a mixture of calcium- and potassiumcaseinate and isolated soy protein as protein source, comprising 9 g/100ml of proteins (16 En %), 12 g/100 ml of fat (48 En %) and 19.7 g/100 mlof digestible carbohydrates (35 En %), and is provided in a 250 ml unitdosage.

The commercially available product FRESUBIN® 2.0 is a high calorieproduct from Fresenius (2 kcal/ml), based on milk proteins as proteinsource, comprising 10 g/100 ml of proteins (20 En %), 7.8 g/100 ml offat (35 En %), and 22.5 g/100 ml of digestible carbohydrates (45 En %),and is provided in a 200 ml unit dosage.

The commercially available product PRO-CAL SHOT® is a high calorieproduct from Vitaflo International Ltd (3.34 kcal/ml), based on skimmedmilk powder and sodium caseinate as protein source, comprising 6.7 g/100ml of proteins (8 En %), 28.2 g/100 ml of fat (76 En %), and 13.4 g/100ml of digestible carbohydrates (16 En %), and is provided in a 250 mlunit dosage.

The commercially available product TwoCal® HN is a high calorie productfrom Abbott Laboratories (Ross Nutrition) (2 kcal/ml), based on sodiumand calcium caseinate as protein source, comprising 8.4 g/100 ml ofproteins (16.7 En %), 8.9 g/100 ml of fat (40.1 En %), and 21.6 g/100 mlof digestible carbohydrates (43.2 En %), and is provided in a 237 mlunit dosage.

SUMMARY OF THE INVENTION

The present invention provides a liquid enteral nutritional compositionwith a high energy content, designed to meet the nutritional needs ofpersons in need thereof, in particular elderly and patients with certaindisease states. The composition provides an increased amount of energyper unit volume while providing a sufficiently low viscosity to allowthe composition to be easily consumed orally or be administered by tube.In addition, the taste of the composition is not diminished.

To this end, in a first aspect of the present invention, a liquidenteral nutritional composition is provided comprising 6 to 14 g ofprotein per 100 ml of the composition, said protein including micellarcasein and caseinate, the composition having an energy density of atleast 2.0 kcal/ml.

In a specific embodiment, a liquid enteral nutritional composition isprovided comprising 6 to 14 g of protein per 100 ml of the composition,said protein including micellar casein, caseinate and whey, thecomposition having an energy density of at least 2.0 kcal/ml.

In particular, a liquid enteral nutritional composition is providedcomprising protein that provides 10% to 30% of the total energy contentof the composition, said protein including micellar casein andcaseinate, the composition having an energy density of at least 2.0kcal/ml.

In a specific embodiment, a liquid enteral nutritional composition isprovided comprising protein that provides 10% to 30% of the total energycontent of the composition, said protein including micellar casein,caseinate and whey, the composition having an energy density of at least2.0 kcal/ml.

Micellar casein, also named native micellar casein, is a high qualitymilk protein and naturally occurring in milk in a concentration of about2.6 g/100 ml (Dairy Science and Technology, Walstra et al., CRC Press,2006). It is concentrated by a process that does not, or does notsubstantially denature the casein proteins and it is marketed asMicellar Casein Isolate (MCI). Fresh skim milk is subjected to afiltration process, in much the same process used to concentrate wheyprotein, to produce a pure, substantially undenaturated milk proteinwith its native structure. The resulting material contains more than 95weight % micellar casein, the rest mainly being whey protein and othernon-protein nitrogen and other constituents, such as lactose. It has anintrinsic low viscosity and a liquid composition comprising said MCI istherefore easy to drink.

In contrast, casein, as it is used in the context of this inventionrefers to the curd form of casein, having lost its native micellarstructure.

Within the context of this invention, it is understood that micellarcasein may also be provided by other milk protein sources, such as, forinstance, sources with essentially preserve the natural 80:20 ratio ofcasein to whey, such as Milk Protein Concentrate (MPC), which is apowder product usually prepared by ultrafiltration with an averageprotein content of about 80 weight %, Milk Protein Isolate (MPI), apowder product usually prepared by precipitation with an average proteincontent of more than 85 weight %, and skimmed concentrated milk.

Although the composition of the present embodiment should not containlarge amounts of proteins other than micellar casein and caseinate, itwas found that the composition of the present invention may comprise upto about 30 weight % of whey protein based on total protein withoutsubstantially affecting the viscosity and shelf-stability, even afterpasteurisation and/or sterilisation.

A problem associated with the use of micellar casein in the productionof liquid enteral nutritional compositions with a high protein contentand further containing acids, in particular citric acid, is theformation of calcium-acid complexes, such as calcium citrate. Inparticular citric acid is added to the composition to adjust the pH andalso to adjust Ca-ion activity. A certain Ca-ion activity is beneficialto maintain a desired viscosity of the composition during processing ofthe composition, e.g. during pasteurisation and/or sterilisation.Calcium, originating from the micellar casein tends to react with acid,in particular the citric acid, thus forming calcium citrate crystals,which precipitate when the acidity of the composition increases overtime (pH lowering), giving rise to a poor shelf stability. Already at apH of 6.9, the formation of Ca-citrate crystals is progressing. On theother hand, a certain Ca-ion activity is beneficial to maintain adesired viscosity of the composition during processing of thecomposition, e.g. during pasteurisation and/or sterilisation. Inparticular a certain Ca-ion activity is beneficial to prevent aviscosity increase during heating. Thus, besides shelf stability, it isa problem to arrive at a proper viscosity when using micellar casein.These problems have now surprisingly been solved by the inventors by amixture of micellar casein and caseinate. Surprisingly, the viscosity ofthe final composition is not increased as much as could be expected bythe substitution of an amount of micellar casein by the same amount ofcaseinate, such that a composition is obtained after heat-treatment withstill a low viscosity, which is still very easy to drink or toadminister by tubing, while at the same time no undesired Ca-acidprecipitates are observed. By heat-treatment is meant any commontreatment known to the skilled person to pasteurise or sterilise thecomposition of the present invention, in the manufacture of anutritional composition, such as defined below.

In a second aspect, the present invention concerns a method of providingnutrition to a person in need thereof, comprising the steps ofadministering to said person the nutritional composition according tothe present invention.

In a third aspect, the present invention concerns the use of a mixtureof micellar casein and, caseinate, and according to a specificembodiment micellar casein, caseinate and whey in the manufacture of aliquid nutritional composition according to the present invention forproviding nutrition to a person.

The invention will now be further elucidated by describing the preferredembodiments of the present invention.

DETAILED DESCRIPTION OF THE INVENTION Protein

According to one embodiment of the present invention, a liquid enteralnutritional composition is provided comprising 6 to 14 g of protein per100 ml of the composition, preferably 8 to 14 g/100 ml of thecomposition, more preferably 8 to 12 g/100 ml of the composition, saidprotein including micellar casein and caseinate, in particular micellarcasein, caseinate and whey, the composition having an energy density ofat least 2.0 kcal/ml.

According to another embodiment of the present invention, the proteinprovides 10% to 30%, preferably 12% to 20%, more preferably 14% to 18%,at least 15% of the total energy content of the composition. The % oftotal energy is also abbreviated as En %; En % is thus short for energypercentage and represents the relative amount that a constituentcontributes to the total caloric value of the composition. In anotherembodiment of the present invention, the protein provides at least 16%of the total energy content. The high levels of protein are beneficialfor patients who may not be physically capable of receiving a largevolume, for example, fluid restricted patients. Such patients can begiven a reduced level of fluid while still receiving a required amountof nutritional support per day.

In the context of this application, the term “at least” also includesthe starting point of the open range. For example, an amount of “atleast 95 weight %” means any amount equal to 95 weight % or above.

In the context of this application, enteral means orally or by tube.

In the context of this application, the nutritional compositionaccording to the invention is heat-treated in order to make thecomposition suitable for commercial use, i.e. the nutritionalcomposition according to the invention is subjected to a heat-treatmentsuch as pasteurisation or sterilisation such that the microbacterialload is reduced.

In one embodiment of the present invention, the composition has anenergy density of at least 2.0 kcal/ml, preferably at least 2.2 kcal/ml,more preferably at least 2.3 kcal/ml, even more preferably at least 2.4kcal/ml. Although the composition has a high energy density, it also hasa sufficiently low viscosity to allow it to be consumed by persons thatmay have difficulty swallowing products or those that are tube fed.

In one embodiment of the present invention, the combined amount ofmicellar casein and caseinate in the liquid nutritional compositionaccording to the invention is at least 70 weight %, more preferably atleast 85 weight %, more preferably at least 90 weight %, more preferablyat least 95 weight % of the total protein present in the liquidnutritional composition.

In another embodiment of the present invention, the combined amount ofmicellar casein, caseinate and whey in the liquid nutritionalcomposition according to the invention is at least 90 weight %, morepreferably at least 95 weight % of the total protein present in theliquid nutritional composition.

As aforementioned, the composition of the present invention should notcontain large amounts of proteins other than micellar casein andcaseinate. However, in a further embodiment of the present invention,the composition may comprise up to about 30 weight % of whey, or lessthan or equal to 20 weight % of whey, or less than or equal to 15 weight% of whey, or less than or equal to 5 weight % of whey of the totalprotein present in the liquid nutritional composition.

In one embodiment of the present invention, Na-caseinate, Mg-caseinate,K-caseinate, Ca-caseinate or any mixture thereof or combinations thereofsuch as Na/K-caseinate and Na/Mg caseinate are used as the source ofcaseinate. Preferably, Ca-caseinate, or a caseinate comprising Ca is notused, as the micellar casein already contains a sufficient amount ofcalcium, and the formation of further calcium crystals should beavoided.

In one embodiment of the present invention, the weight ratio of micellarcasein to caseinate ranges from 90:10 to 35:65. Preferably, the weightratio of micellar casein to caseinate ranges from 80:20 to 40:60.

In another embodiment of the present invention when also an amount ofwhey is present, the weight ratio of micellar casein to whey ranges from95:5 to 70:30. Preferably, the weight ratio of micellar casein to wheyis equal to about 80:20.

The composition according to the invention is designed to eithersupplement a person's diet or to provide complete nutritional support.Hence, the composition according to the invention may further compriseat least fat and/or carbohydrate and/or a source of vitamins andminerals and/or a source of prebiotics. Preferably, the compositionaccording the invention is a nutritionally complete composition.

Fat

In one embodiment of the present invention, the liquid nutritionalcomposition according to the invention further comprises fat, said fatproviding between 20 to 40% of the total energy content of thecomposition. For a 2.0 kcal/ml composition, this amounts to 40 to 80kcal per 100 ml.

With regard to the type of fat, a wide choice is possible, as long asthe fat is of food quality.

The fat may either be an animal fat or a vegetable fat or both. Althoughanimal fats such as lard or butter have essentially equal caloric andnutritional values and can be used interchangeably, vegetable oils arehighly preferred in the practice of the present invention due to theirreadily availability, ease of formulation, absence of cholesterol andlower concentration of saturated fatty acids. In one embodiment, thepresent composition comprises rapeseed oil, corn oil and/or sunfloweroil.

The fat may include a source of medium chain fatty acids, such as mediumchain triglycerides (MCT, mainly 8 to 10 carbon atoms long), a source oflong chain fatty acids, such as long chain triglycerides (LCT) andphospholipid-bound fatty acids such as phospholipid-bound EPA or DHA, orany combination of the two types of sources. MCTs are beneficial becausethey are easily absorbed and metabolized in a metabolically-stressedpatient. Moreover, the use of MCTs will reduce the risk of nutrientmalabsorption. LCT sources, such as canola oil, rapeseed oil, sunfloweroil, soybean oil, olive oil, coconut oil, palm oil, linseed oil, marineoil or corn oil are beneficial because it is known that LCTs maymodulate the immune response in the human body.

In one specific embodiment, the fat comprises 30 to 60 weight % ofanimal, algal or fungal fat, 40 to 70 weight % of vegetable fat andoptionally 0 to 20 weight % of MCTs based on total fat of thecomposition. The animal fat preferably comprises a low amount of milkfat, i.e. lower than 6 weight %, especially lower than 3 weight % basedon total fat. In particular, a mixture of corn oil, egg oil, and/orcanola oil and specific amounts of marine oil are used. Egg oils, fishoils and algal oils are a preferred source of non-vegetable fats.Especially for compositions that are to be consumed orally, in order toprevent formation of off-flavours and to decrease a fishy after-taste,it is recommended to select ingredients that are relatively low indocosahexanoic acid (DHA), i.e. less than 6 weight %, preferably lessthan 4 weight % based on total fat. Marine oils containing DHA arepreferably present in the composition according to the invention in anamount lower than 25 weight %, preferably lower than 15 weight % basedon total fat. On the other hand, inclusion of eicosapentanoic acid (EPA)is highly desirable for obtaining the maximum health effect. Therefore,in another embodiment, the amount of EPA may range between 4 weight %and 15 weight %, more preferably between 8 weight % and 13 weight %based on total fat. The weight ratio EPA:DHA is advantageously at least6:4, for example between 2:1 and 10:1. In yet another embodiment, theamount of EPA is very low, such as 0.1 to 1 weight %, preferably 0.3weight % or 0.6 weight %, based on total fat.

Also, the liquid nutritional composition according to the invention maybeneficially comprise an emulsifier. Commonly known emulsifiers may beused and generally the emulsifier contributes to the energy content ofthe fat in said composition.

Digestible Carbohydrate

In one embodiment of the present invention, the liquid nutritionalcomposition according to the invention further comprises digestiblecarbohydrate, said digestible carbohydrate providing between 30 to 60%of the total energy content of the composition. For a 2.0 kcal/mlcomposition, this amounts to 80 to 120 kcal per 100 ml. Preferably, thedigestible carbohydrate provides at least 40% of the total energycontent of the composition according to the invention. The digestiblecarbohydrate may comprise either simple or complex carbohydrates, or anymixture thereof. Suitable for use in the present invention are glucose,fructose, sucrose, lactose, trehalose, palatinose, corn syrup, malt,maltose, isomaltose, partially hydrolysed corn starch, maltodextrins,glucose oligo- and poly-saccharides.

The composition of the digestible carbohydrate preferably is such thathigh viscosities, excessive sweetness, excessive browning (Maillardreactions) and excessive osmolarities are avoided. Acceptableviscosities and osmolarities may be achieved by adjusting the averagechain length (average degree of polymerisation, DP) of the digestiblecarbohydrates between 1.5 and 6, preferably between 1.8 and 4. In orderto avoid excessive sweetness, the total level of sucrose and fructose isless than 52% and preferably less than 40% of the weight of thecarbohydrate, especially of the digestible carbohydrate. Long-chaindigestible carbohydrates such as starch, starch fractions and mildstarch hydrolysates (DP≧6, DE<20), may also be present, preferably in anamount of less than 25 weight %, especially less than 15 weight % of thedigestible carbohydrate, and less than 6 g/100 ml, preferably less than4 g/100 ml of the total liquid enteral composition according to theinvention.

In one embodiment of the present invention, the digestible carbohydrateincludes maltodextrose with a high DE (dextrose equivalent). In oneembodiment the digestible carbohydrate includes maltodextrose with a DEof >20, preferably >30 or even >40, such as a DE of about 47.Surprisingly, the use of maltodextrose leads to few or no Maillardreaction products upon heating. Without being bound to any explanation,this effect might be attributed to the fact that the compact micellarstructure of the micellar casein offers few lysine reaction sites for aMaillard reaction. In one embodiment of the present invention, thedigestible carbohydrate includes maltodextrose with a high DE in anamount of at least 35 weight %, preferably at least 50 weight %,preferably at least 65 weight %, preferably at least 90 weight % of thetotal weight of digestible carbohydrate. In one embodiment of thepresent invention, the digestible carbohydrate includes maltodextrosewith a low DE of 2 to 20. In one embodiment of the present invention,the digestible carbohydrate includes maltodextrose with a low DE of 2 to10, preferably with a low DE of about 2. In one embodiment of thepresent invention, the digestible carbohydrate includes maltodextrosewith a low DE in an amount of less than 35 weight %, preferably lessthan 20 weight %, preferably less than 10 weight % of the digestiblecarbohydrate. Maltodextrose with a low DE may also be referred to asmaltodextrine. In another embodiment of the present invention, thedigestible carbohydrate includes maltodextrose with a high DE,preferably a DE of >20, preferably >30 or even >40, most preferably a DEof about 47 in combination with maltodextrose with a low DE, preferablya low DE of 2 to 20, more preferably a low DE of 2 to 10, mostpreferably with a low DE of about 2. As is known, maltodextrose with alow DE, such as of about 2, gives rise to a high viscosity.Maltodextrose with a high DE, such as of about 47 gives rise to a lowviscosity, but is very sweet. The combination of both maltodextrosesoptimizes the balance between sweetness and viscosity. In one embodimentof the present invention, the digestible carbohydrate includes at least65 weight %, preferably at least 90 weight %, based on total weight ofdigestible carbohydrate of maltodextrose with a DE>40, preferably with aDE of about 47 and 0 to 10 weight % of maltodextrose with a DE 2 to 10,preferably with a DE of about 2.

In another embodiment of the present invention, the digestiblecarbohydrate includes trehalose. As was indicated, it is one of the mainobjects of the invention to provide a nutritional composition with a lowviscosity. Sucrose is very well suited for such purpose, but gives riseto very sweet compositions, which are in general disliked by theconsumer. Maltodextrose with a low DE, such as of about 2, does notsuffer from the latter drawback, but gives rise to a high viscosity.Maltodextrose with a high DE, such as of about 47 gives rise to a lowviscosity, but is again very sweet, and gives further rise to theundesired Maillard reactions. Trehalose is a preferred choice ofdigestible carbohydrate, as it gives rise to a low viscosity, noundesired Maillard reactions and it has a sweetness about half of thatof sucrose. In one embodiment of the present invention, the digestiblecarbohydrate includes trehalose in an amount of 20% to 60% of the weightof the digestible carbohydrate, in an amount of 20% to 45%, morepreferably in an amount of 25% to 45% of the weight of the digestiblecarbohydrate.

Vitamins and Minerals

The composition according to the invention may contain a variety ofvitamins and minerals. Overall, the composition according to theinvention preferably includes at least 100% of the United StatesRecommended Daily Allowance (USRDA) of vitamins and minerals in a onelitre portion.

In one embodiment of the present invention, the composition according tothe invention provides all necessary vitamins and minerals. For example,the composition according to the invention preferably provides 6 mg ofzinc per 100 ml of the composition which is beneficial for tissue repairin a healing patient. Preferably, the composition according to theinvention (also) provides 25 mg of vitamin C per 100 ml of thecomposition to aid patients with more severe healing requirements.Further, preferably, the composition according to the invention (also)provides 2.25 mg iron per 100 ml of the composition. Iron is beneficialin maintaining bodily fluids as well as circulatory system functions inan elderly patient.

In another embodiment of the present invention, the amount of divalentions ranges between 170 mg/100 ml and 230 mg/100 ml and preferablybetween 180 mg/100 ml and 220 mg/100 ml. Preferably, the amount ofcalcium ranges between 155 mg/100 ml and 185 mg/100 ml and preferablybetween 160 mg/100 ml and 180 mg/100 ml. The phosphorus content can beabove 10 mg per g of protein, with a calcium to phosphorus weight ratiobetween 1.0 and 2.0, preferably between 1.1 and 1.7. Carnitin mayadvantageously be present in an amount of 8 mg/100 ml to 1000 mg/100 ml,preferably 10 mg/100 ml to 100 mg/100 ml of composition; it may have theform of carnitin, alkyl carnitin, acyl carnation or mixtures thereof.Organic acids are preferably present at a level of between 0.1 g/100 mlto 0.6 g/100 ml, especially 0.25 g/100 ml to 0.5 g/100 ml. These acidsinclude short fatty acids such as acetic acid, hydroxy acids such aslactic acid, gluconic acid, and preferably polyvalent hydroxy acids,such as malic acid and citric acid. In one embodiment of the presentinvention, the present composition also comprises citric acid.

Non-Digestible Carbohydrates

The liquid enteral nutritional composition according to the inventionmay optionally be fortified with non-digestible carbohydrates (dietaryfibres) such as fructo-oligosaccharides or inulin. In an embodiment ofthe present invention, the composition according to the inventioncomprises 0.5 g/100 ml to 6 g/100 ml of non-digestible carbohydrates.The dietary fibres include non-digestible oligosaccharides having a DPof 2 to 20, preferably 2 to 10. More preferably, these oligosaccharidesdo not contain substantial amounts (less than 5 weight %) of saccharidesoutside these DP ranges, and they are soluble. These oligosaccharidesmay comprise fructo-oligosaccharides (FOS),trans-galacto-oligosaccharides (TOS), xylo-oligosaccharides (XOS), soyoligosaccharides, and the like. Optionally, also higher molecular weightcompounds such as inulin, soy polysaccharides, acacia polysaccharides(acacia fibre or arabic gum), cellulose, resistant starch and the likemay be incorporated in the composition according to the invention. Theamount of insoluble fibre such as cellulose is preferably lower than 20weight % of the dietary fibre fraction of the composition according tothe invention, and/or below 0.6 g/100 ml. The amount of thickeningpolysaccharides such as carrageenans, xanthans, pectins, galactomannansand other high molecular weight (DP>50) indigestible polysaccharides ispreferably low, i.e. less than 20% of the weight of the fibre fraction,or less than 1 g/100 ml. Instead, hydrolysed polysaccharides such ashydrolysed pectins and galactomannans can advantageously be included.

A preferred fibre component is an indigestible oligosaccharide with achain length (DP) of 2 to 10, for example Fibersol® (resistantoligoglucose), in particular hydrogenated Fibersol®, or a mixture ofoligosaccharides having a DP of 2 to 10, such as fructo-oligosaccharidesor galacto-oligosaccharides, which may also contain a small amount ofhigher saccharides (e.g. with a DP of 11 to 20). Such oligosaccharidespreferably comprise 50 weight % to 90 weight % of the fibre fraction, or0.5 g/100 ml to 3 g/100 ml of the composition according to theinvention. Other suitable fibre components include saccharides that haveonly partial digestibility.

In a particular embodiment, the composition according to the inventioncomprises one or more of fructo-oligosaccharides, inulin, acaciapolysaccharides, soy polysaccharaides, cellulose and resistant starch.

In another embodiment of the present invention, the compositionaccording to the invention may comprise a mixture of neutral and acidoligosaccharides as disclosed in WO 2005/039597 (N.V. Nutricia), whichis incorporated herein by reference in its entirety. More in particular,the acid oligosaccharide has a degree of polymerisation (DP) between 1and 5000, preferably between 1 and 1000, more preferably between 2 and250, even more preferably between 2 and 50, most preferably between 2and 10. If a mixture of acid oligosaccharides with different degrees ofpolymerisation is used, the average DP of the acid oligosaccharidemixture is preferably between 2 and 1000, more preferably between 3 and250, even more preferably between 3 and 50. The acid oligosaccharide maybe a homogeneous or heterogeneous carbohydrate. The acidoligosaccharides may be prepared from pectin, pectate, alginate,chondroitine, hyaluronic acids, heparine, heparane, bacterialcarbohydrates, sialoglycans, fucoidan, fucooligosaccharides orcarrageenan, and are preferably prepared from pectin or alginate. Theacid oligosaccharides may be prepared by the methods described in WO01/60378, which is hereby incorporated by reference. The acidoligosaccharide is preferably prepared from high methoxylated pectin,which is characterised by a degree of methoxylation above 50%. As usedherein, “degree of methoxylation” (also referred to as DE or “degree ofesterification”) is intended to mean the extent to which free carboxylicacid groups contained in the polygalacturonic acid chain have beenesterified (e.g. by methylation). The acid oligosaccharides arepreferably characterised by a degree of methoxylation above 20%,preferably above 50% even more preferably above 70%. Preferably the acidoligosaccharides have a degree of methylation above 20%, preferablyabove 50% even more preferably above 70%. The acid oligosaccharide ispreferably administered in an amount of between 10 mg and 100 gram perday, preferably between 100 mg and 50 grams per day, even more between0.5 and 20 gram per day.

The term neutral oligosaccharides as used in the present inventionrefers to saccharides which have a degree of polymerisation of monoseunits exceeding 2, more preferably exceeding 3, even more preferablyexceeding 4, most preferably exceeding 10, which are not or onlypartially digested in the intestine by the action of acids or digestiveenzymes present in the human upper digestive tract (small intestine andstomach) but which are fermented by the human intestinal flora andpreferably lack acidic groups. The neutral oligosaccharide isstructurally (chemically) different from the acid oligosaccharide. Theterm neutral oligosaccharides as used in the present inventionpreferably refers to saccharides which have a degree of polymerisationof the oligosaccharide below 60 monose units, preferably below 40, evenmore preferably below 20, most preferably below 10. The term monoseunits refers to units having a closed ring structure, preferably hexose,e.g. the pyranose or furanose forms. The neutral oligosaccharidepreferably comprises at least 90%, more preferably at least 95% monoseunits selected from the group consisting of mannose, arabinose,fructose, fucose, rhamnose, galactose, β-D-galactopyranose, ribose,glucose, xylose and derivatives thereof, calculated on the total numberof monose units contained therein. Suitable neutral oligosaccharides arepreferably fermented by the gut flora. Preferably the oligosaccharide isselected from the group consisting of: cellobiose(4-O-β-D-glucopyranosyl-D-glucose), cellodextrins((4-O-β-D-glucopyranosyl)_(n)-D-glucose), B-cyclodextrins (Cyclicmolecules of α-1-4-linked D-glucose; α-cyclodextrin-hexamer,β-cyclodextrin-heptamer and γ-cyclodextrin-octamer), indigestibledextrin, gentiooligosaccharides (mixture of β-1-6 linked glucoseresidues, some 1-4 linkages), glucooligosaccharides (mixture ofα-D-glucose), isomaltooligosaccharides (linear α-1-6 linked glucoseresidues with some 1-4 linkages), isomaltose(6-O-α-D-glucopyranosyl-D-glucose); isomaltriose(6-O-α-D-glucopyranosyl-(1-6)-α-D-glucopyranosyl-D-glucose), panose(6-O-α-D-glucopyranosyl-(1-6)-α-D-glucopyranosyl-(1-4)-D-glucose),leucrose (5-O-α-D-glucopyranosyl-D-fructopyranoside), palatinose orisomaltulose (6-O-α-D-glucopyranosyl-D-fructose), theanderose(O-α-D-glucopyranosyl-(1-6)-O-α-D-glucopyranosyl-(1-2)-B-D-fructofuranoside),D-agatose, D-lyxo-hexulose, lactosucrose(O-β-D-galactopyranosyl-(1-4)-O-α-D-glucopyranosyl-(1-2)-β-D-fructofuranoside),α-galactooligosaccharides including raffinose, stachyose and other soyoligosaccharides(O-α-D-galactopyranosyl-(1-6)-α-D-glucopyranosyl-β-D-fructofuranoside),β-galactooligosaccharides or transgalacto-oligosaccharides(β-D-galactopyranosyl-(1-6)-[β-D-glucopyranosyl]_(n)-(1-4) α-D glucose),lactulose (4-O-β-D-galactopyranosyl-D-fructose), 4′-galatosyllactose(O-D-galactopyranosyl-(1-4)-O-β-D-glucopyranosyl-(1-4)-D-glucopyranose),synthetic galactooligosaccharide (neogalactobiose, isogalactobiose,galsucrose, isolactosel, II and III), fructans-Levan-type(β-D-(2→6)-fructofuranosyl)_(n) α-D-glucopyranoside),fructans-Inulin-type (β-D-((2→1)-fructofuranosyl)_(n)α-D-glucopyranoside), 1 f-β-fructofuranosylnystose(β-D-((2→1)-fructofuranosyl)_(n) B-D-fructofuranoside),xylooligosaccharides (B-D-((1→4)-xylose)_(n), lafinose, lactosucrose andarabinooligosaccharides.

According to a further preferred embodiment the neutral oligosaccharideis selected from the group consisting of fructans,fructooligosaccharides, indigestible dextrins galactooligosaccharides(including transgalactooligosaccharides), xylooligosaccharides,arabinooligosaccharides, glucooligosaccharides, mannooligosaccharides,fucooligosaccharides and mixtures thereof. Most preferably, the neutraloligosaccharide is selected from the group consisting offructooligosacchararides, galactooligosaccharides andtransgalactooligosaccharides.

Suitable oligosaccharides and their production methods are furtherdescribed in Laere K. J. M. (Laere, K. J. M., Degradation ofstructurally different non-digestible oligosaccharides by intestinalbacteria:glycosylhydrolases of Bi. adolescentis. PhD-thesis (2000),Wageningen Agricultural University, Wageningen, The Netherlands), theentire content of which is hereby incorporated by reference.Transgalactooligosaccharides (TOS) are for example sold under thetrademark Vivinal™ (Borculo Domo Ingredients, Netherlands). Indigestibledextrin, which may be produced by pyrolysis of corn starch, comprisesα(1→4) and α(1→6) glucosidic bonds, as are present in the native starch,and contains 1→2 and 1→3 linkages and levoglucosan. Due to thesestructural characteristics, indigestible dextrin containswell-developed, branched particles that are partially hydrolysed byhuman digestive enzymes. Numerous other commercial sources ofindigestible oligosaccharides are readily available and known to skilledperson. For example, transgalactooligosaccharide is available fromYakult Honsha Co., Tokyo, Japan. Soybean oligosaccharide is availablefrom Calpis Corporation distributed by Ajinomoto U.S.A. Inc., Teaneck,N.J.

In a further preferred embodiment the composition according to theinvention comprises an acid oligosaccharide with a DP between 2 and 250,prepared from pectin, alginate, and mixtures thereof; and a neutraloligosaccharide, selected from the group of fructans,fructooligosaccharides, indigestible dextrins, galactooligosaccharidesincluding transgalactooligosaccharides, xylooligosaccharides,arabinooligosaccharides, glucooligosaccharides, mannooligosaccharides,fucooligosaccharides, and mixtures thereof.

In a further preferred embodiment the composition according to theinvention comprises two chemically distinct neutral oligosaccharides. Itwas found that the administration of acid oligosaccharides combined withtwo chemically distinct neutral oligosaccharides provides an optimalsynergistic immune stimulatory effect. Preferably the compositionaccording to the invention comprises:

-   -   an acid oligosaccharides as defined above;    -   a galactose-based neutral oligosaccharide (of which more than        50% of the monose units are galactose units), preferably        selected from the group consisting of galactooligosaccharide and        transgalactooligosaccharide; and    -   a fructose and/or glucose based neutral oligosaccharide (of        which more than 50% of the monose units are fructose and/or        glucose, preferably fructose units), preferably inulin, fructan        and/or fructooligosaccharide, most preferably long chain        fructooligosaccharide (with an average DP of 10 to 60).

The mixture of acid- and neutral oligosaccharides is preferablyadministered in an amount of between 10 mg and 100 gram per day,preferably between 100 mg and 25 grams per day, even more preferablybetween 0.5 and 20 gram per day.

Viscosity and Osmolarity

In one embodiment of the present invention, the viscosity of the liquidenteral nutritional composition is lower than 120 mPa·s at 20° C. at ashear rate of 100 s⁻¹, preferably between 80 and 50 mPa·s, preferablylower than 50 mPa·s, more preferably between 20 and 45 mPa·s. Theviscosity may be determined using a rotational viscosity meter using acone/plate geometry.

In another embodiment of the present invention, the protein comprises ofa blend of micellar casein, caseinate and whey, wherein the weight ratioof micellar casein to caseinate ranges from 80:20 to 40:60 and whereinthe weight ratio of micellar casein to whey ranges from 95:5 to 70:30.The latter embodiment of the present invention has a viscosity ofapproximately about 80 mPa·s. This is ideal for orally administering theliquid enteral nutritional composition according to the inventionbecause a person may easily consume a serving having a low viscositysuch as that displayed by the present invention. This is also ideal forunit dosages that are tube fed.

In one embodiment of the present invention, the osmolarity of thecomposition is preferably lower than 900 mOsm/l, more preferably lowerthan 800 mOsm/l, most preferable lower than 700 mOsm/l.

In one embodiment of the present invention, the density of thecomposition ranges between 1.05 g/ml and 1.20 g/ml, especially between1.10 g/ml and 1.18 g/ml.

Dosage Unit

The liquid enteral nutritional composition according to the inventionmay have the form of a complete food, i.e. it can meet all nutritionalneeds of the user. As such, it preferably contains 1200 to 2500 kcal perdaily dosage. The daily dosage amounts are given with respect to a dailyenergy supply of 2000 kcal to a healthy adult having a body weight of 70kg. For persons of different condition and different body weight, thelevels should be adapted accordingly. It is understood that the averagedaily energy intake preferably is about 2000 kcal. The complete food canbe in the form of multiple dosage units, e.g. from 4 (250 ml/unit) to 20(50 ml/unit) per day for an energy supply of 2000 kcal/day using aliquid enteral nutritional composition according to the invention of 2.0kcal/ml.

The liquid enteral nutritional composition can also be a foodsupplement, for example to be used in addition to a non-medical food.Preferably as a supplement, the liquid enteral nutritional compositioncontains per daily dosage less than 1500 kcal, in particular as asupplement, the liquid enteral nutritional composition contains 400 to1000 kcal per daily dose. The food supplement can be in the form ofmultiple dosage units, e.g. from 2 (250 ml/unit) to 10 (50 ml/unit) perday for an energy supply of 1000 kcal/day using a liquid enteralnutritional composition according to the invention of 2.0 kcal/ml.

In one embodiment of the present invention, a unit dosage comprises anyamount of the liquid enteral nutritional composition according to theinvention between 10 ml and 250 ml, the end values of this rangeincluded, preferably any amount between 25 ml and 200 ml, the end valuesof this range included, more preferably any amount between 50 ml and 150ml, the end values of this range included, most preferably about 125 ml.For example, a person receiving 50 ml unit dosages can be given 10 unitdosages per day to provide nutritional support using a liquid enteralnutritional composition according to the invention of 2.0 kcal/ml.Alternatively a person receiving 125 ml unit dosages can be given 4 or 5or 6 or 7 or 8 unit dosages per day to provide nutritional support usinga liquid enteral nutritional composition according to the invention of2.0 kcal/ml. Such small dosage units are preferred because of bettercompliance.

In one embodiment of the present invention, the composition is providedin a ready to use liquid form and does not require reconstitution ormixing prior to use. The composition according to the invention can betube fed or administered orally. For example, the composition accordingto the invention can be provided in a can, on spike, and hang bag.However, a composition may be provided to a person in need thereof inpowder form, suitable for reconstitution using an aqueous solution orwater such that the composition according to the invention is produced.Thus in one embodiment of the present invention, the present compositionis in the form of a powder, accompanied with instructions to dissolve orreconstitute in an aqueous composition or water to arrive at the liquidnutritional enteral composition according to the present invention. Inone embodiment of the present invention, the present liquid nutritionalenteral composition may thus be obtained by dissolving or reconstitutinga powder, preferably in an aqueous composition, in particular water.

In one embodiment of the present invention, the composition according tothe invention is packaged. The packaging may have any suitable form, forexample a block-shaped carton, e.g. to be emptied with a straw; a cartonor plastic beaker with removable cover; a small-sized bottle for examplefor the 80 ml to 200 ml range, and small cups for example for the 10 mlto 30 ml range. Another suitable packaging mode is inclusion of smallvolumes of liquid (e.g. 10 ml to 20 ml) in edible solid or semi-solidhulls or capsules, for example gelatine-like coverings and the like.Another suitable packaging mode is a powder in a container, e.g. asachet, preferably with instructions to dissolve or reconstitute in anaqueous composition or water.

Preparation

The liquid enteral nutritional composition according to the inventionmay be prepared by first preparing the liquid protein composition. Thismay be done by sequentially or simultaneously dissolving micellar caseinin powder form and caseinate in powder form in water. It is alsopossible to use micellar casein in a wet form, directly prepared frommilk. It may even be advantageous to prepare the micellar casein as apart of a continuous process to prepare the composition according to theinvention. The latter may be done in the same production facility toprepare the composition according to the invention.

Furthermore, if the liquid enteral nutritional composition is to containfurther components, a nutritional product may be prepared bysubsequently adding the carbohydrates to the protein composition,followed by adding the water-soluble vitamins and other components inone or two stages, mixing, adjusting the resulting composition to thedesired viscosity, adding the fat, including fat-soluble vitamins,homogenizing, subjecting the resulting solution to a heat-treatment(pasteurization, sterilisation) and packaging the resulting product. Inthis respect, it is noted that the acidity of the composition is veryimportant during the heat-treatment. The pH should be between about 6.6and 7.2 for the pasteurisation and sterilisation. Typical pasteurisationtimes are 30 sec at 85° C. Typical sterilisation times are 4 minutes at124° C.

In the embodiment where micellar casein, caseinate and whey is presentin the formulation according to the invention, it was found favorablenot to pasteurise but only to sterilise the formulation according to theinvention.

Effectivity

The present invention also concerns a method of providing nutrition to aperson in need thereof, comprising the steps of administering to saidperson the nutritional composition according to the present invention.Said person may be an elderly person, a person that is in a diseasestate, a person that is recovering from a disease state, or a personthat is malnourished.

In a further aspect, the present invention also concerns thesimultaneous or sequential use of micellar casein and caseinate in themanufacture of a liquid nutritional composition according to the presentinvention for providing enteral nutrition to a person in need thereof.In one particular embodiment of the present invention, said compositionprovides 6 to 14 g of protein per 100 ml of composition, said proteinincluding micellar casein, caseinate and optionally whey, thecomposition having an energy density of at least 2.0 kcal/ml. In anotherparticular embodiment of the present invention, said protein provides10% to 30% of the total energy content of the composition, thecomposition having an energy density of at least 2.0 kcal/ml.

In one embodiment, the present invention concerns a liquid enteralnutritional composition comprising:

a) about 9.6 g of protein per 100 ml of the composition of a mixture ofmicellar casein and caseinate, with a weight ratio of micellar casein tocaseinate of about 65:35, said protein providing about 16% of the totalenergy content of the composition;b) fat providing about 35% of the total energy content of thecomposition;c) carbohydrate providing about 49% of the total energy content of thecomposition, said composition having an energy density of about 2.4kcal/ml.

In another embodiment, the present invention concerns a liquid enteralnutritional composition comprising:

a) about 9.6 g of protein per 100 ml of the composition of a mixture ofmicellar casein, caseinate and whey with a weight ratio micellarcasein:caseinate:whey of about 44:45:11, said protein providing about16% of the total energy content of the composition;b) fat providing about 35% of the total energy content of thecomposition;c) carbohydrate providing about 49% of the total energy content of thecomposition, said composition having an energy density of about 2.4kcal/ml.

In yet another embodiment, the present invention concerns a liquidenteral nutritional composition comprising:

a) about 9.6 g of protein per 100 ml of the composition of a mixture ofmicellar casein, caseinate and whey with a weight ratio micellarcasein:caseinate:whey of about 63:21:16, said protein providing about16% of the total energy content of the composition;b) fat providing about 35% of the total energy content of thecomposition;c) carbohydrate providing about 49% of the total energy content of thecomposition, said composition having an energy density of about 2.4kcal/ml.

Examples

The following composition according to the invention has been prepared(Table 1). The composition is produced in a manner known per se, e.g. bymixing the ingredients, without difficulties, is shelf-stable, hasdesirable organoleptic properties, has a very high nutrient density andis effective for a person in need thereof.

It should be understood that various changes and modifications to thepresently preferred embodiments described herein will be apparent tothose skilled in the art. Such changes and modifications may be madewithout departing from the spirit and scope of the invention and withoutdiminishing its advantages.

Notes to the Table

-   -   Skim concentrated milk contains about 13.3% of micellar casein        and whey in a ratio of about 80:20.    -   Milk Protein Isolate contains about 89% of micellar casein and        whey in a ratio of about 80:20.

Micellar Casein Isolate contains about 89% of micellar casein and wheyin a ratio of about 95:5.

TABLE 1 Amount per Amount per Amount per Amount per Amount per Amountper Amount per 100 ml of 100 ml of 100 ml of 100 ml of 100 ml of 100 mlof 100 ml of Component product product product product product productproduct Energy 240 kcal 240 kcal 240 kcal 240 kcal 240 kcal 240 kcal 240kcal Protein 16.0 En %   16.0 En %   16.0 En %   16.0 En %   16.0 En %  16.0 En %   16.0 En %   Protein 9.6 g 9.6 g 9.6 g 9.6 g 9.6 g 9.6 g 9.6g Skim concentrated milk* — 4.07 g 4.07 g 3.49 g 3.49 g — — Potassiumcaseinate — 2.71 g 2.64 g 2.11 g 2.11 g — — Calcium caseinate — 1.66 g —— — — — Sodium-caseinate 3.3 g — — — — 3.3 g 3.3 g Milk Protein Isolate*— 1.25 g 3.04 g 4.11 g — — — Micellar Casein Isolate* 6.3 g — — — 4.11 g6.3 g 6.3 g Native micellar casein 6.0 4.26 5.68 6.08 6.70 6.0 6.0Caseinate 3.3 4.37 2.64 2.11 2.11 3.3 3.3 Whey 0.3 1.06 1.42 1.52 0.900.3 0.3 Fat 35 En % 35 En % 35 En % 35 En % 35 En % 35 En % 35 En % Fatmainly comprising canola oil 9.3 g 9.3 g 9.3 g 9.3 g 9.3 g 9.3 g 9.3 gCarbohydrates 49 En % 49 En % 49 En % 49 En % 49 En % 49 En % 49 En %maltodextrose (DE47) 29.4 g 29.4 g 29.4 g 29.4 g 29.4 g 9.8 g 9.8 gsucrose — — — — — 9.8 g 9.8 g trehalose — — — — — 9.8 g 9.8 g DietaryFibre — — — — — 0.9 g GOS 1.23 g inuline 0.1 g lcFOS 1.72 g FOS 0.2 glow 0.41 g cellulose viscosity pectin 0.086 g resistant starch Viscosity(mPa · s at 20° C. at 70 mPa · s 110 mPa · s 80 mPa · s 80 mPa · s 75mPa · s — — 100 s⁻¹) Density 1.16 g/ml 1.16 g/ml 1.16 g/ml 1.16 g/ml1.16 g/ml — — Unit dosage 125 ml 125 ml 125 ml 125 ml 125 ml 125 ml 125ml Minerals and vitamines are added as 16% of RDI.

1.-26. (canceled)
 27. A heat-treated liquid enteral nutritionalobtainable by heat-treating a liquid enteral nutritional compositionhaving an energy density of at least 2.0 kcal/ml and comprising 8 to 14g of protein per 100 ml of the composition, said protein providing10-30% of the total energy content of the composition, wherein saidcomposition comprises a combined amount of micellar casein, caseinateand whey of at least 95 weight % of total protein.
 28. The liquidenteral nutritional composition according to claim 27, wherein themicellar casein and whey protein are provided by milk proteinconcentrate, and wherein said composition comprises 5-15 wt % wheyprotein, based on total protein.
 29. The liquid enteral nutritionalcomposition according to claim 27, wherein the micellar casein and wheyprotein are provided by milk protein concentrate, and wherein saidcomposition comprises 5-10 wt % whey protein, based on total protein.30. The liquid enteral nutritional composition according to claim 27,the protein consisting of micellar casein, caseinate and whey.
 31. Theliquid enteral nutritional composition according to claim 28, theprotein consisting of milk protein concentrate and caseinate.
 32. Theliquid enteral nutritional composition according to claim 27, whereinthe composition has an energy density of at least 2.4 kcal/ml.
 33. Theliquid enteral nutritional composition according to claim 27, whereinthe caseinate is Na-caseinate, Ca-caseinate, Mg-caseinate, K-caseinateor any mixture or combination thereof.
 34. The liquid enteralnutritional composition according to claim 27, said protein providing15-30% of the total energy content of the composition.
 35. The liquidenteral nutritional composition according to claim 27, furthercomprising fat, the fat providing between 20 to 40% of the total energycontent of the composition.
 36. The liquid enteral nutritionalcomposition according to claim 27, further comprising carbohydrate, thecarbohydrate providing between 30 to 60% of the total energy content ofthe composition.
 37. The liquid enteral nutritional compositionaccording to claim 27, further comprising acids.
 38. The liquid enteralnutritional composition according to claim 27, wherein the compositionis sterilized and/or pasteurized.
 39. The liquid enteral nutritionalcomposition according to claim 27, wherein the composition issterilized.
 40. The liquid enteral nutritional composition according toclaim 27, wherein the composition comprises at least 85 weight % of thecombination of micellar casein and caseinate.
 41. The liquid enteralnutritional composition according to claim 27, wherein the compositioncomprises between 155 and 185 mg/100 ml calcium.
 42. A method ofproviding nutrition to a person in need thereof, comprisingadministering to the person a composition according to claim
 27. 43. Themethod according to claim 42, wherein the person in need thereof is anelderly person having an age of 50 years or more, a person that is in adisease state, a person that is recovering from a disease state, or aperson that is malnourished.
 44. A method for manufacturing aheat-treated liquid enteral nutritional composition, comprising (i)providing a liquid enteral nutritional composition having an energydensity of at least 2.0 kcal/ml and comprising 8 to 14 g of protein per100 ml of the composition, said protein providing 10-30% of the totalenergy content of the composition, wherein said composition comprises acombined amount of micellar casein, caseinate and whey of at least 95weight % of total protein, and (ii) heat-treating said composition. 45.The method according to claim 44, wherein the composition is sterilizedand/or pasteurized.
 46. The method according to claim 44, wherein thecomposition is sterilized.
 47. The method according to claim 44, whereinthe protein provides between 15 to 30% of the total energy content ofthe composition.
 48. The method according to claim 44, wherein themicellar casein and whey protein are provided by milk proteinconcentrate, and wherein said composition comprises 5-10 wt % wheyprotein, based on total protein.
 49. The method according to claim 44,the protein consisting of micellar casein, caseinate and whey.
 50. Themethod according to claim 48, the protein consisting of milk proteinconcentrate and caseinate.
 51. The method according to claim 44, whereinthe composition has an energy density of at least 2.4 kcal/ml.
 52. Themethod according to claim 44, wherein the composition comprises at least85 weight % of a combination of micellar casein and caseinate.